Basic and Translational ScienceGene Expression Profile During Testicular Development in Patients With SRY-negative 46,XX Testicular Disorder of Sex Development
Section snippets
Ethics Statement
Studies using human testicular tissue were carried out after obtaining written informed consent from the families of the patients and the approval of the Institutional Review Board of Nagoya City University Hospital (approval number 83). All animal experimental procedures were performed in accordance with protocols approved by the Animal Care Committee of Nagoya City University Graduate School of Medical Sciences (protocol number: H23M-20).
Patients and Sample Preparation
We had previously examined 5 patients with 46,XX
Results
The patient with 46,XX testicular DSD analyzed herein presented with hypospadias and bilateral cryptorchidism, and multiple surgeries were performed. Peripheral blood sample analysis revealed no expression of SRY or DAZ genes in this patient using by fluorescence in situ hybridization methods. We further investigated the testicular tissue of this patient and age-matched XY tissue derived from the patient with hydrocele. Histologic findings of XX and XY testes are shown in Figure 1A, B. Both the
Comment
The mechanisms mediating testicular development in SRY-negative 46,XX testicular DSD patients, such as the patient presented in this study, remain unclear. In the present study, we investigated the differential expression of genes between XX and XY testes using PCR-based subtractive hybridization and detected 13 upregulated genes in XX testes. In this study, we confirmed the overexpression of the ROCK1 gene and found that the expression of ROCK1 protein was increased in Sertoli cells of XX
Conclusion
We identified ROCK1 as the differentially expressed gene between XX and XY testes. ROCK1 protein was detected in the germ cells and Sertoli cells. On the basis of the results of in vitro inhibition assay, we hypothesized that ROCK1 phosphorylates and activates SOX9 in Sertoli cells. It is suggested that testis formation is initiated by an alternative signaling pathway attributed to ROCK1, and not SRY, activation in 46,XX testicular DSD.
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Elucidation of distinctive genomic DNA structures in patients with 46,XX testicular disorders of sex development using genome wide analyses
2014, Journal of UrologyCitation Excerpt :Fetal (embryonic day 17) and juvenile (postcoital day 12) testes were removed and fixed in 4% paraformaldehyde or Bouin solution and then embedded in paraffin to enable histological examination. Signals were detected with a 1:500 dilution of S7443 anti-SOX3 antibody (Sigma-Aldrich®), as described previously.5 Studies using human genomic material were performed only after obtaining written informed consent from the families of the patients and Nagoya City University Hospital review board approval (No. 83).
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Financial Disclosure: The authors declare that they have no relevant financial interests.
Funding Support: This article was supported by funding from a Grant-in-Aid for Scientific Research (B) of Japan Society for the Promotion of Science (40238134).